A Preliminary Attempt to Personalize Risperidone Dosing Using Drug–Drug Interactions and Genetics: Part I

• Published in: Psychosomatics (Washington, D.C.) D.C.), 2008-05, Vol.49 (3), p.258-270
• Main Authors: de Leon, Jose, M.D, Sandson, Neil B., M.D, Cozza, Kelly L., M.D
• Format: Article
• Language: English
• Subjects: Antipsychotic Agents - administration & dosage; Antipsychotic Agents - pharmacokinetics; Antipsychotic Agents - therapeutic use; Binding Sites - drug effects; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Cytochrome P-450 CYP2D6 - genetics; Drug Administration Schedule; Drug Interactions; Genotype; Humans; Internal Medicine; Medical sciences; Neuropharmacology; Patient-Centered Care; Pharmacology. Drug treatments; Polymorphism, Genetic - genetics; Psychiatry; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Receptors, Adrenergic - drug effects; Receptors, Adrenergic - genetics; Receptors, Dopamine D2 - drug effects; Receptors, Dopamine D2 - genetics; Receptors, Dopamine D2 - metabolism; Receptors, Histamine - drug effects; Receptors, Histamine - genetics; Receptors, Serotonin - drug effects; Receptors, Serotonin - genetics; Risperidone - administration & dosage; Risperidone - pharmacokinetics; Risperidone - therapeutic use; Schizophrenia - drug therapy; Schizophrenia - genetics
• ISSN: 0033-3182; 1545-7206
• DOI: 10.1176/appi.psy.49.3.258

Background Personalized prescription is described even in lay journals, but there has been no attempt to propose personalizing dosing for any specific psychiatric drug. Objective Any attempt to develop personalized dosing needs to be anchored in our understanding of the pharmacological response of each drug in each person’s environment, particularly drug–drug interactions (DDIs) and how genetic make-up influences drug response. Method Risperidone (R) is used as an example. R’s pharmacologic response is reviewed in detail by focusing on our current knowledge of its pharmacodynamic and pharmacokinetic actions. The influences of the environment and genetics on these two actions are reviewed. Results R’s antipsychotic action is probably mainly explained by the blocking of dopamine receptors, particularly D2 receptors. There are polymorphic variations of this gene (DRD2 ), but it is not clear that they have clinical relevance in predicting adverse drug reactions (ADRs) or antipsychotic response. Conclusion Previous exposure to antipsychotics increases the need for higher R dosing, but the mechanism for this tolerance is not well understood. Other brain receptors, such as other dopamine, serotonin, and adrenergic receptors may explain some of these ADRs. Some polymorphic variations in these receptors have been described, but they cannot yet be used to personalize R dosing.